Method Development of Pegmolesatide for Doping Analysis: A Novel Synthetic Erythropoietin-Mimetic Agent.

IF 2.6 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Drug Testing and Analysis Pub Date : 2025-07-17 DOI:10.1002/dta.3931

Lu Liu, Zhanliang Wang, Lingyu Zhao, Xinmiao Zhou, Lisi Zhang

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引用次数: 0

Abstract

Pegmolesatide, a novel synthetic erythropoietin-mimetic agent, was developed by the Hansoh Pharmaceutical Manufacturing Company Ltd. (Jiangsu, China). In late 2023, it was approved in China for the treatment of anemia in both dialysis and non-dialysis patients with chronic kidney disease, with the advantages of reduced immunogenicity and extended duration of action. The aim of this study was to develop a strategy for detecting pegmolesatide in doping analysis. Here, we present a bottom-up nano-liquid chromatography-high-resolution tandem mass spectrometry approach for qualitative analysis of pegmolesatide using erythropoietin receptor coupled magnetic beads, followed by trypsinization and subsequent detection of characteristic peptides. Using full scan and data-dependent MS/MS (ddMS2) modes, two characteristic peptide segments of pegmolesatide were identified. An analytical method using product ion scan mode was developed to detect the identified characteristic peptides. Both peptide segments were analyzed for the initial testing procedure, whereas one characteristic peptide segment obtained from complete trypsinization was analyzed for the confirmation procedure. After full validation, the selectivity, reliability, limit of detection, limit of identification, carryover, and stability were evaluated. The results demonstrate that our developed method can be a fit-for-purpose analytical method for the antidoping of pegmolesatide.

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方法：一种新型人工合成促红细胞生成素兴奋剂聚莫苷的研制。

Pegmolesatide是中国江苏汉索制药有限公司研制的一种新型人工合成促红细胞生成素类药物。2023年底，它在中国被批准用于治疗透析和非透析慢性肾病患者的贫血，具有降低免疫原性和延长作用时间的优点。本研究的目的是开发一种在兴奋剂分析中检测聚莫苷的策略。在这里，我们提出了一种自下而上的纳米液相色谱-高分辨率串联质谱方法，使用促红细胞生成素受体偶联磁珠对聚莫苷进行定性分析，然后进行胰蛋白酶化和随后的特征肽检测。采用全扫描和数据依赖的MS/MS （ddMS2）模式，鉴定了聚莫塞肽的两个特征肽段。建立了一种利用产物离子扫描模式检测鉴定出的特征肽的分析方法。两个肽段被分析用于初始测试程序，而从完全胰蛋白酶化中获得的一个特征肽段被分析用于确认程序。充分验证后，对选择性、信度、检出限、鉴别限、携带性和稳定性进行评价。结果表明，该方法是一种适合于吡莫苷反兴奋剂分析的方法。

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来源期刊

Drug Testing and Analysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

5.90

自引率

24.10%

发文量

191

审稿时长

2.3 months

期刊介绍： As the incidence of drugs escalates in 21st century living, their detection and analysis have become increasingly important. Sport, the workplace, crime investigation, homeland security, the pharmaceutical industry and the environment are just some of the high profile arenas in which analytical testing has provided an important investigative tool for uncovering the presence of extraneous substances. In addition to the usual publishing fare of primary research articles, case reports and letters, Drug Testing and Analysis offers a unique combination of; ‘How to’ material such as ‘Tutorials’ and ‘Reviews’, Speculative pieces (‘Commentaries’ and ‘Perspectives'', providing a broader scientific and social context to the aspects of analytical testing), ‘Annual banned substance reviews’ (delivering a critical evaluation of the methods used in the characterization of established and newly outlawed compounds). Rather than focus on the application of a single technique, Drug Testing and Analysis employs a unique multidisciplinary approach to the field of controversial compound determination. Papers discussing chromatography, mass spectrometry, immunological approaches, 1D/2D gel electrophoresis, to name just a few select methods, are welcomed where their application is related to any of the six key topics listed below.